Preparations of collagen have found use in a variety of therapeutic and reconstructive contexts in both soft tissue and bone, as well as in the preparation of surgical sponges and associated accessories for medical use.
Collagen is the major protein of the skeletal system, and is found in bone, skin, and cartilage. Native collagen consists in large part of a triple helical structure which appears to be a consequence of repeating triplet sequences composed of glycine linked to two additional amino acids, commonly proline and hydroxyproline, the glycine being in every third position in the chain. In addition, all collagen chains contain regions at each end which do not have the triplet glycine sequence and are thus not helical. These regions are thought to be responsible for the immunogenicity associated with most collagen preparations, and this property can, in large part, be mitigated by removal of these regions to produce "atelopeptide" collagen. The removal can be accomplished by digestion with proteolytic enzymes such as trypsin or pepsin. These non-helical atelopeptide regions are however, required to form the cross-links which are responsible for stability of the fibrillar structure in native collagen, since they contain aldehydes capable of cross-linkage; atelopeptide collagen must be cross-linked artificially if it is desired to obtain this characteristic.
Starting from the native material, derived either from bone or from skin, a variety of approaches to the preparation of pure collagenous materials has been disclosed. For example, Battista, U.S. Pat. No. 3,471,598 and 3,632,361 discloses the preparation of a collagen sponge which is a partial salt formed by preparing a dispersion of the collagen salt in an aqueous medium, casting into a mold and freeze drying. This approach is different from that disclosed in U.S. Pat. No. 3,157,524 which describes a collagen reconstituted by reprecipitation of a solubilized tropocollagen (the basic molecular triple helical unit) from a solution. In addition, commercial preparations commonly known as "Collagenfleece" (U.S. Pat. No. 4,066,083) and Avitene provide relatively pure, contiguous collagen preparations which, however, contain atelopeptides and are often immunogenic.
Other preparations of collagen are available commercially. Prominent among these is Zyderm.RTM. collagen implant (ZCI) which is a reconstituted fibrillar suspension of atelopeptide collagen. This preparation is usable in augmenting soft tissue (U.S. Pat. No. 4,424,208) and for cosmetic purposes (when provided as a suspension (U.S. Pat. No. 4,140,537)). The nature of the application to which the collagen preparation is to be put is, of course, instrumental in determining the form of collagen which is most desirable. Certain properties such as, for example, non-immunogenicity are common as desirable to all medical applications. However, other desirable properties vary. For construction of bone replacement material, for example, it would be preferable to have a malleable contiguous mass, whereas for cosmetic "wrinkle-smoothing" applications, an injectable suspension would be preferred. Thus, it is beneficial to provide an arsenal of collagen preparation types whose characteristics offer a spectrum of physical properties.
The present invention adds to the repertoire of available physical properties associated with non-immunogenic collagen preparation.